The role of the vitamin K-dependent amino acid, gamma-carboxyglutamic acid, in calcium binding and protein-membrane interaction will be investigated. The ultimate goal is the elucidation of the precise molecular basis for calcium binding and protein-membrane interaction by this amino acid. In order to understand this interaction, studies on the phospholipid and on the proteins (e.g., prothrombin) are planned. These studies will be conducted in the presence and absence of divert cations which constitute an essential third component of the protein-membrane interaction. Studies on the membrane will include the possible role of calcium-induced lateral phase separations and the function of phospholipid dimerization. The important protein structures will be determined by techniques such as modification of specific amino acids, peptide chain cleavage (and partial sequence analysis), NMR analysis of protein structures altered by calcium, etc. The biosynthesis of sialic acid-containing proteins will be investigated and attempts will be made to alter sialic acid distribution by administering sialic acid precursors or enzyme inhibitors. The goal of this research is the understanding of the functions of the carbohydrate portion of glycoproteins.